Management of Actinic Keratosis.

Management of actinic keratosis.

Drug Ther Bull. 2013 Jul 4;

Actinic keratoses are common, often multiple, epidermal lesions found mainly on the sun-exposed skin of fair-skinned middle-aged and older people.(1) Over time, lesions may remain unchanged or may proliferate, regress, reappear or develop into squamous cell carcinoma (SCC).(2) Detectable (spot) lesions are often associated with alteration of the surrounding skin (field) where subclinical lesions might be present.(2) Interventions may target individual or multiple lesions or a whole field.(2) Here, we update our previous review(3) on the prevention and treatment of actinic keratoses, focusing on the licensed treatments most commonly used in the UK and recommended in UK guidelines. HubMed – drug


Comparison of Three Methods (An Updated Logistic Probabilistic Method, the Naranjo and Liverpool Algorithms) for the Evaluation of Routine Pharmacovigilance Case Reports Using Consensual Expert Judgement as Reference.

Drug Saf. 2013 Jul 5;
Théophile H, André M, Miremont-Salamé G, Arimone Y, Bégaud B

An updated probabilistic causality assessment method and the Liverpool algorithm presented as an improved version of the Naranjo algorithm, one of the most used and accepted causality assessment methods, have recently been proposed.In order to test the validity of the probabilistic method in routine pharmacovigilance, results provided by the Naranjo and Liverpool algorithms, as well as the updated probabilistic method, were each compared with a consensual expert judgement taken as reference.A sample of 59 drug-event pairs randomly sampled from spontaneous reports to the French pharmacovigilance system was assessed by expert judgement until reaching consensus and by members of a pharmacovigilance unit using the updated probabilistic method, the Naranjo and Liverpool algorithms. Probabilities given by the probabilistic method, and categories obtained by both the Naranjo and the Liverpool algorithms were compared as well as their sensitivity, specificity, positive and negative predictive values.The median probability for drug causation given by the consensual expert judgement was 0.70 (inter-quartile range, IQR 0.54-0.84) versus 0.77 (IQR 0.54-0.91) for the probabilistic method. For the Naranjo algorithm, the ‘possible’ causality category was predominant (61 %), followed by ‘probable’ (35 %), ‘doubtful’, and ‘almost certain’ categories (2 % each). Category distribution obtained with the Liverpool algorithm was similar to that obtained by the Naranjo algorithm with a majority of ‘possible’ (61 %) and ‘probable’ (30 %) followed by ‘definite’ (7 %) and ‘unlikely’ (2 %). For the probabilistic method, sensitivity, specificity, positive and negative predictive values were 0.96, 0.56, 0.92 and 0.71, respectively. For the Naranjo algorithm, depending on whether the ‘possible’ category was considered in favour or in disfavour of drug causation, sensitivity was, respectively, 1 or 0.42, specificity 0.11 or 0.89, negative predictive value 1 or 0.22 and positive predictive value 0.86 or 0.95; results were identical for the Liverpool algorithm.The logistic probabilistic method gave results closer to the consensual expert judgment than either the Naranjo or Liverpool algorithms whose performance were strongly dependent on the meaning given to the ‘possible’ category. Owing to its good sensitivity and positive predictive value and by providing results as continuous probabilities, the probabilistic method seems worthy to use for a trustable assessment of adverse drug reactions in routine practice. HubMed – drug


Identifying Associations between Maternal Medication Use and Birth Defects Using a Case-Population Approach: An Exploratory Study on Signal Detection.

Drug Saf. 2013 Jul 5;
de Jonge L, Zetstra-van der Woude PA, Bos HJ, de Jong-van den Berg LT, Bakker MK

The effects of many drugs on the unborn child are unknown. In a case-population design, drug exposure of cases is compared with that of a source population; this kind of study can be useful for generating signals.To see whether a comparison of drug use rates from the birth defect registry EUROCAT NNL (cases) with prescription rates from a population-based prescription database, the IADB (population), could be used to detect signals of teratogenic risk of drugs.We defined 3,212 cases from the EUROCAT NNL database, a population-based birth defect registry in the Northern Netherlands and 29,223 population controls from the IADB, a prescription database with data from community pharmacies in the same geographical area, born between 1998 and 2008. We classified the malformations of the 3,212 cases into several malformation groups according to organ system (based on the International Classification of Diseases codes and the EUROCAT guidelines). If a child had multiple malformations in several organ systems (n = 253, 7.9 %), he/she was counted in all the categories represented. For several groups of malformations we calculated rate ratios (RR) and 95 % confidence intervals for drugs acting on the central nervous system and for drugs considered to be safe for use in pregnancy. The RRs were based on first-trimester drug use rates from the cases in the EUROCAT NNL database and prescription rates from the population controls in the IADB.For drugs acting on the central nervous system we found significantly increased RRs for the anti-epileptic drug valproic acid and for some selective serotonin reuptake inhibitors. For drugs considered to be safe only the anti-hypertensive methyldopa showed significantly increased RRs.We show that a case-population study is a suitable method for detecting signals of possible teratogenicity, provided that the teratogenic effects and the drugs under study are as specific as possible and the drugs are widely used. HubMed – drug


Neutrophil Dynamics in Peritoneal Carcinomatosis Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Oxaliplatin.

Clin Pharmacokinet. 2013 Jul 5;
Pérez-Ruixo C, Valenzuela B, Peris JE, Bretcha-Boix P, Escudero-Ortiz V, Farré-Alegre J, Pérez-Ruixo JJ

Peritoneal carcinomatosis is an abdominal metastatic manifestation of a life-threatening tumour progression requiring standard palliative surgery and/or chemotherapy treatment. The aim of this study was to characterize the immediate neutrophilia response induced by cytoreductive surgery (CRS) and the myelosuppression effect of hyperthermic intraperitoneal oxaliplatin (HIO) in peritoneal carcinomatosis patients.Absolute neutrophil counts (ANCs) from 45 patients treated with CRS and HIO diluted in isotonic 4 % icodextrin (cohort A), 21 patients undergoing CRS followed by HIO diluted in isotonic 5 % dextrose (cohort B) and 18 patients treated with CRS without HIO (cohort C) were used to estimate the system-related parameters [baseline ANC (Circ0), mean transit time (MTT) and feedback on proliferation (?)] and drug-specific (?) parameters of a modified Friberg’s model that accounts for the surgical stress-induced neutrophilia. The plasma oxaliplatin concentrations, C p, were assumed to reduce the proliferation rate of the progenitor cells according to the function ? × C p. Model evaluation and simulations were undertaken to evaluate the effect of the dose, treatment duration and carrier solution on the incidence of severe neutropenia.The typical values [between-subject variability, expressed in coefficient of variation values (%)] of the Circ0, MTT, ? and ? were estimated to be 3.58 × 10(9) cells/L (41.2 %), 144 h (70.9 %), 0.155 and 0.066 L/mg (134.9 %), respectively. Surgical stress induced a maximal 3.37-fold increase in the proliferation rate that was attenuated with a half-life of 10 days, and a maximal 68 % reduction in the MTT that was attenuated with a half-life of 28 days. Age, body surface area, sex, total proteins and carrier solution did not impact the model parameters. The model evaluation evidenced an accurate prediction of the incidence of neutropenia grade ?2 and/or ?3. Simulations indicated that (i) the neutropenia was reversible and short-lasting; and (ii) the HIO dose and treatment duration were the main determinants of the severity and duration of neutropenia.The time course of neutropenia was well characterized by the model that was developed, which simultaneously accounts for the acute-immediate neutrophilia response induced by CRS and the HIO myelosuppressive effect produced in the bone marrow. This model suggests that higher doses than those evaluated to date could be used in peritoneal carcinomatosis patients without substantially increasing the risk of severe neutropenia. HubMed – drug